琥珀酰明胶注射液对脓毒症大鼠A2B腺苷受体介导的肺毛细血管通透性的影响

摘要

目的 研究不同剂量琥珀酰明胶注射液(改良明胶,MFG)对A2B腺苷受体(A2BAR)介导的肺毛细血管通透性的影响.方法 50只雄性SD大鼠,随机分为五组,每组10只,假手术组(S组):不结扎,不穿孔,不复苏；生理盐水组(NS组,30 ml/kg);输注MFG 7.5 ml/kg组(MFG1组)；15 ml/kg组(MFG2组);30 ml/kg组(MFG3组).大鼠盲肠结扎穿孔(CLP)术后4h开始液体复苏2h,6h内持续监测HR和MAP,6h后处死动物取相应组织进行检测:肺毛细血管通透性、A2BAR含量、cAMP及PKA表达水平、TNF-α、IL-6和IL-10含量.结果 与S组比较,NS、MFG1、MFG2、MFG3组肺毛细血管通透性、A2BAR表达、cAMP及PKA、TNF-α、IL-6和IL-10含量均升高(P＜0.05或P＜0.01).与NS组比较,MFG组肺毛细血管通透性均降低(P＜0.05)；A2BAR表达,cAMP及PKA含量均升高(P＜0.05或P＜0.01).TNF-α,IL-6和IL-10含量差异无统计学意义.结论 MFG可通过增强内皮细胞上A2BAR的表达及其信号通路的传导来发挥其肺血毛细血管保护作用.%Objective To investigate the effects of different doses of modified fluid Gelatin (MFG) on the protection of pulmonary capillary permeability mediated by A2B adenosine receptor (A2BAR) in a rat model of sepsis. Methods Fifty male SD rats weighing 250-300 g were randomly divided into 5 groups (n=10 each); sham group (group S): abdomen was opened and closed, without cecal ligation; sepsis groups(group NS) were induced by cecal ligation and puncture (CLP). Group MFG1, MFG2 and MFG3 groups were respectively received MFG7. 5, 15 and 30 ml/kg and group NS received NS 30 ml/kg 4 h after CLP. All of the animals were killed humanly at 6 h after surgery for determination of pulmonary capillary permeability, A2BAR, cAMP, PKA expression, and inflammatory cytokines levels in the lung. Results Compared with group S, pulmonary permeability, A2BAR, cAMP and PKA, TNF-α, IL-6 and IL-10 were all increased in the rest groups (P<0. 01). Compared with group NS, there were no different in TNF-α, IL-6 and IL-10, pulmonary permeability were decreased, A2BAR, cAMP and PKA were all increased in the group MFG1, MFG2 and MFG3 (P<0. 05 or P<0. 01). Conclusion MFG may decrease pulmonary permeability by increasing the expression of A2BAR and up-regulating its signal transduction in pulmonary.